Our studies have concerned regulation of gene expression during normal and abnormal differentiation processes. Topics of current interest are: 1) control of expression of Alpha-fetoprotein (AFP), albumin, and transferrin in liver and liver derived cell lines; 2) control of expression of human chorionic gonadotropin (hCG) and alkaline phosphatase in placental, normal and malignant nontrophoblastic cells. Using the temperature-sensitive rat fetal liver cells, we have demonstrated that both qualitative and quantitative alternations in AFP gene experssion occurred during transformation of fetal liver cells in vitro. At 40 C, RLA209-15 fetal liver cells exhibit a differentiated phenotype that resemble fetal liver in vivo: they synthesize two AFP variants of 73,000 and 69,000 daltons and contain an AFP mRNA species of 20S. RLA209-15 cells exhibit a transformed phenotype at 33 C. Transformation is accompanied by the synthesis of reduced level of AFP with an apparent molecular weight of 65,000 and the detection of reduced level of AFP mRNA of 14S. The 14S AFP mRNA appears to be generated by the alternative RNA splicing pathway. The RLA209-15 cells also prove to be a suitable model system to study the molecular basis of maturation. We found that retinoic acid is one of the regulators that induce maturation of fetal liver in vitro. In studies on alkaline phosphatase gene expression, we found that both sodium butyrate and 5-bromo-2'deoxyuridine (BrdUrd) induce a specific increase in the placental alkaline phosphatase mRNA leading to the observed enhancement of biosynthesis.